IP Library › Granted Patent US 12678432
Granted Patent B2
US 12678432 · App. 17/780,512 · Granted Jul 14, 2026

Substituted crotonamide pharmaceutical composition and preparation method therefor

Inventors: Haitao Tang (Nanjing, CN); Bei Wang (Nanjing, CN); Bin Ge (Nanjing, CN); Haitao Ge (Nanjing, CN); Zhengjun Wang (Nanjing, CN)
Assignee: Jiangsu Medolution Ltd
A61K31/4709A61K9/485A61K9/4858A61K9/4866A61K31/4706
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12678432
App. No.
17/780,512
Granted
Jul 14, 2026
Kind
B2
Abstract

A composition of substituted crotonamide pharmaceutical and a preparation method therefor. The pharmaceutical composition comprises 5-50 parts of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate, 40-120 parts of a filler, 2-20 parts of a disintegrant, 0-6 parts of an adhesive, and 0.5-5 parts of a lubricant. The filler is selected from carbohydrates.

Claims (18)

1 . A pharmaceutical composition comprising (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate or hydrate thereof, wherein the pharmaceutical composition comprises: 5-50 mg of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate or hydrate thereof, 40-200 mg of a filler, 2-20 mg of a disintegrant which is sodium carboxymethyl starch, 0-6 mg of a binder which is hydroxypropyl cellulose, and 0.5-8 mg of a lubricant which is glyceryl behenate.

2 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises: 8-20 mg of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate or hydrate thereof, 50-200 mg of the filler, 4-20 mg of sodium carboxymethyl starch, 0.3-5 mg of hydroxypropyl cellulose, and 0.5-8 mg of glyceryl behenate.

3 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises: 8-20 mg of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate or hydrate thereof, 130-200 mg of the filler, 10-20 mg of sodium carboxymethyl starch, 1-3 mg of hydroxypropyl cellulose, and 1-8 mg of glyceryl behenate.

4 . The pharmaceutical composition according to claim 1 , wherein the filler is a sugar alcohol.

5 . The pharmaceutical composition according to claim 4 , wherein the sugar alcohol is selected from the group consisting of mannitol, xylitol, sorbitol, and lactose.

6 . The pharmaceutical composition according to claim 5 , wherein the sugar alcohol is mannitol.

7 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises: 8-20 mg of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate monohydrate.

8 . The pharmaceutical composition according to claim 7 , wherein a water content in the pharmaceutical composition is 5 wt % or less.

9 . The pharmaceutical composition according to claim 8 , wherein a water content in the pharmaceutical composition is 1.5 wt % or less.

10 . The pharmaceutical composition according to claim 7 , further comprising an impurity compound represented by Formula (II):

11 . The pharmaceutical composition according to claim 10 , wherein when exposed to 75% relative humidity at 40°° C. for 3 months, the pharmaceutical composition comprises the impurity compound represented by Formula (II) at no more than 0.47% as measured by High Performance Liquid Chromatography (HPLC).

12 . The pharmaceutical composition according to claim 10 , wherein when exposed to 75% relative humidity at 40° C. for 3 months, the pharmaceutical composition comprises the impurity compound represented by Formula (II) at no more than 0.22% as measured by HPLC.

13 . The pharmaceutical composition according to claim 7 , wherein the filler is selected from the group consisting of mannitol, xylitol, sorbitol, and lactose.

14 . The pharmaceutical composition according to claim 13 , wherein the filler is mannitol.

15 . The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition comprises: 8-20 mg of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate monohydrate, 130-200 mg of mannitol, 10-20 mg of sodium carboxymethyl starch, 1-3 mg of hydroxypropyl cellulose, 1-8 mg of glyceryl behenate, and an impurity compound represented by Formula (II):

16 . A pharmaceutical composition comprising: about 8.4 wt % to 11.6 wt % of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino) quinolin-6-yl)-4-(dimethylamino) but-2-enamide maleate or hydrate thereof, about 75.6 wt % to 84 wt % of a filler that is mannitol or lactose, from 4.2 wt % to 11.6 wt % of sodium carboxymethyl starch, about 0.5 wt % to 1.3 wt % of hydroxypropyl cellulose, and from 0.6 wt % to 4.0 wt % of glyceryl behenate.

17 . The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises: about 8.4 wt % to 11.6 wt % of (E)-N-(3-cyano-7-ethoxy-4-(3-ethynylphenylamino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide maleate monohydrate.

18 . The pharmaceutical composition according to claim 16 , further comprising an impurity compound represented by Formula (II):